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  • 1.
    Lima da Cruz, Rafael Vitor
    et al.
    Univ Fed Rio Grande do Norte, Brain Inst, Neurodynam Lab, Natal, RN, Brazil.
    Moulin, Thiago C.
    Univ Fed Rio de Janeiro, Inst Med Biochem, Rio De Janeiro, Brazil.
    Petiz, Lyvia Lintzmaier
    Univ Fed Rio Grande do Norte, Brain Inst, Neurodynam Lab, Natal, RN, Brazil.
    Leão, Richardson N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics. Univ Fed Rio Grande do Norte, Brain Inst, Neurodynam Lab, Natal, RN, Brazil.
    A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus2018In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 11, article id 312Article in journal (Refereed)
    Abstract [en]

    The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation. We show that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, using a transgenic animal expressing tamoxifen-dependent Cre recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had a higher number of newborn DG Granule cells (GC). We also showed that these DG GC have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.

  • 2.
    Moulin, Thiago C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology. Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Petiz, Lyvia L.
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Rayêe, Danielle
    Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
    Winne, Jessica
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Maia, Roberto G.
    Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
    Lima da Cruz, Rafael V.
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Amaral, Olavo B.
    Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazi.
    Leão, Richardson N.
    Brain Institute, Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil.
    Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology, and Hebbian plasticity in the mouse hippocampus2019In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 29, no 8, p. 755-761Article in journal (Refereed)
    Abstract [en]

    Prolonged increases in excitation can trigger cell‐wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes, and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 hr of stimulation with 15‐ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin‐2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2‐expressing mice immediately after the end of stimulation. Finally, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.

  • 3.
    Moulin, Thiago
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Rayee, Danielle
    Maia, Roberto
    Freitas, Jéssica
    Lima, Rafael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Brain Institute - UFRN.
    Petiz, Lyvia
    Leão, Richardson
    Amaral, Olavo
    Chronic in vivo optogenetic stimulation modulates Hebbian plasticity and spine density in the mouse hippocampus2018In: biorxivArticle in journal (Other academic)
    Abstract [en]

    Continuous excitation can trigger cell-wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely-moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, and (b) lead to alterations in Hebbian plasticity. After 24 h of stimulation with 15-ms blue light pulses every 90 s, dendritic spine density was reduced in the CA1 region of mice expressing channelrhodopsin-2 (ChR2) when compared to controls. This protocol also impaired the induction of LTP and facilitated that of LTD in ex vivo slices obtained from ChR2-expressing mice immediately after the end of stimulation. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.

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